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Efficient viral expression of a chemogenetic receptor in the old-world monkey amygdala

Lookup NU author(s): Dr Mark EldridgeORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2023. Genetically encoded synthetic receptors, such as the chemogenetic and optogenetic proteins, are powerful tools for functional brain studies in animals. In the primate brain, with its comparatively large, intricate anatomical structures, it can be challenging to express transgenes, such as the hM4Di chemogenetic receptor, in a defined anatomical structure with high penetrance. Here, we compare parameters for lentivirus vector injections in the rhesus monkey amygdala. We find that four injections of 20 μl, infused at 0.5 μl/min, can achieve neuronal hM4Di expression in 50–100% of neurons within a 60 mm3 volume, without observable damage from overexpression. Increasing the number of hM4Di_CFP lentivirus injections to up to 12 sites per hemisphere, resulted in 30%–40% neuronal coverage of the overall amygdala volume, with coverage reaching 60% in some subnuclei. Manganese Chloride was mixed with lentivirus and used as an MRI marker to verify targeting accuracy and correct unsuccessful injections in these experiments. In a separate monkey we visualized, in vivo, viral expression of the hM4Di receptor protein in the amygdala, using Positron Emission Tomography. Together, these data show efficient and verifiable expression of a chemogenetic receptor in old-world monkey amygdala.

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Author(s): Lerchner W, Dash K, Rose D, Eldridge MAG, Rothenhoefer KM, Yan X, Costa VD, Averbeck B, Richmond BJ

Publication type: Article

Publication status: Published

Journal: Current Research in Neurobiology

Year: 2023

Volume: 4

Online publication date: 31/05/2023

Acceptance date: 16/05/2023

Date deposited: 19/02/2025

ISSN (electronic): 2665-945X

Publisher: Elsevier BV

URL: https://doi.org/10.1016/j.crneur.2023.100091

DOI: 10.1016/j.crneur.2023.100091

Data Access Statement: Full dataset can be accessed at: Mendeley Data, V1, doi: 10.17632/x8jh23yzvb.1

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